This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ebola virus causes a severe hemorrhagic disease in humans and non-human primates (NHP). In humans, the disease is fatal in up to 90% of infected individuals, depending on the Ebola virus species involved in the outbreak. Currently there are neither licensed vaccines nor therapies to prevent or treat Ebola virus. The usual preventive public health measures cannot be applied in the case of Ebola hemorrhagic fever because the natural reservoir has not been positively identified. In light of the risk of bioterrorism and recurrent Ebola outbreaks in Africa, the development of an effective Ebola virus vaccine is urgently needed. Because traditional human efficacy trials cannot be performed for candidate Ebola virus vaccines, licensure will have to be obtained by the Food and Drug Administration's 'Animal Rule'which requires demonstration of efficacy in nonhuman primates. Significant progress has been made towards developing an Ebola vaccine based on DNA and recombinant adenovirus virus vectors. The objective of this study is to test adeno based Ebola vaccines and immunization strategies in nonhuman primates to identify/define immune correlates of protection. Blood samples will be obtained from animals injected with vaccines for assessment of specific vaccine-induced immune responses. Vaccines and unvaccinated controls will be exposed to a lethal dose of Ebola virus to determine the efficacy of candidate vaccines. Animals vaccinated with candidate vaccines will be protected from exposure to a lethal dose of Ebola virus, whilst unvaccinated controls will succumb to infection. The results obtained from these studies will be important in supporting licensure of an Ebola vaccine for clinical application.